We are not alone. Currently, over 500 species of bacteria live in your mouth. Each part of your gut (stomach, small intestine, large intestine) is home to 1000 unique bacterial species. Many more bacteria live on your skin and in every orifice in your body. Microbes make up (at least half of) who we are. We are a walking ecosystem with an incredible diversity of organisms unique to us, and in more ways than one, they make up who we are and what we do.
This “cloud” of microbes that lives in and on us (called the “microbiome”) provides essential functions for our well-being. Microbes help to digest our food, produce valuable nutrients, and prevent the growth of “bad” bacteria from harming us. In exchange, we provide the bacteria with a warm, humid, protected place to live. What a deal!
But could there be a role of the microbiome in autoinflammatory diseases, given that most of these diseases are genetically determined?
Let’s look at familial Mediterranean fever (FMF), the most common inherited autoinflammatory disease. In medical school, I learned that FMF is a genetic disease that requires inheriting two mutated copies of the MEFV (MEditerranean FeVer) gene. However, this theory does not fully explain what I actually see in practice. First, many patients with FMF have only one mutated gene –and some patients with FMF have no mutated genes at all! Second, if FMF is a genetic disease, and you always carry the faulty genes with you, why does it often take many years for patients to develop their first symptoms of FMF? Third, what triggers the attacks, and what makes them go away? Finally, why is the severity of FMF dependent on the country where you live?
It is possible that the microbiome helps to explain some of these differences. Researchers have known for years that if you are an Armenian with FMF living in Armenia, your disease is more severe than if you were living in the US. Similarly, a Turkish patient living in Turkey has a more severe disease than a Turkish patient in Germany.
More recently, researchers have also shown that the country where you live helps to determine the composition of your microbiome: if you live in Venezuela, for example, you will have a different microbiome than if you lived in Vermont. Your microbiome also changes as you age.
An interesting theory from mice
Last month, a study of autoinflammatory disease in mice showed a remarkable effect of diet and the microbiome on disease severity. These mice inherit two mutated copies of a gene that causes a disease similar to the human autoinflammatory disease chronic recurrent multifocal osteomyelitis. When fed a normal low-fat diet, all mice develop the disease. However, researchers found that if they instead feed the mice a high-fat diet, it changes their microbiome and they don’t get sick! In addition, by transferring bacteria between healthy and diseased mice (via a fecal transplant), researchers could “give” the disease to some mice, while “protecting” others.
In these mice, it seems that diet determines the variety of bacteria that grow in the gut, and this mix of bacteria determines how much inflammation is produced in the gut, determining whether the mice will develop the disease.
What this study shows is that even though the mice were genetically determined to develop an autoinflammatory disease, whether or not they actually developed the disease depended on their diet, and in turn, on their gut microbiome.
Whether diet and the microbiome can have such powerful effects on the severity of human autoinflammatory diseases such as FMF remains to be seen.
What do you think? Have you noted that your diet or country of residence influenced the severity of your autoinflammatory disease?
Interested in seeing how I wrote this essay? Take a look at my Slow TV video to find out exactly how it was done!
